The oscillatory responses of skate electroreceptors to small voltage stimuli.

Tonic nerve activity in skate electroreceptors is thought to result from spontaneous activity of the lumenal membranes of the receptor cells which is modulated by applied stimuli. When physiological conditions are simulated in vitro, the receptor epithelium produces a current which flows inward across the lumenal surface. This epithelial current exhibits small spontaneous sinusoidal fluctuations about the mean that are associated with corresponding but delayed fluctuations in postsynaptic response. Small voltage stimuli produce damped oscillations in the epithelial current similar in time-course to the spontaneous fluctuations. For lumen-negative, excitatory stimuli, these responses are predominantly an increase over the mean inward current. For inhibitory stimuli they are predominantly a decrease. Increased inward current across the lumenal membranes of the receptor cells increases depolarization of the presynaptic membranes in the basal faces leading to increased release of transmitter and an excitatory postsynaptic response. Decreased inward current decreases depolarization of the presynaptic membranes leading to a reduction in transmitter release and an inhibitory postsynaptic response. Clear changes in postsynaptic response are detectable during stimuli as small as 5 microV with saturation occurring at +/- 400 microV. The evoked oscillations in epithelial current are damped and the postsynaptic responses decline during maintained stimuli with large off-responses occurring at stimulus termination. The initial peak of the off-response is similar to the response produced by onset of an oppositely directed stimulus. These observations substantiate the role of receptor cell excitability in the detection of small voltage changes.

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Enhanced phosphorylation of Na+–Cl− co-transporter in experimental metabolic syndrome: role of insulin

Clinical Science ◽

10.1042/cs20120003 ◽

2012 ◽

Vol 123 (11) ◽

pp. 635-647 ◽

Cited By ~ 38

Author(s):

Radko Komers ◽

Shaunessy Rogers ◽

Terry T. Oyama ◽

Bei Xu ◽

Chao-Ling Yang ◽

...

Keyword(s):

Metabolic Syndrome ◽

Time Course ◽

Kinase Inhibitor ◽

Endogenous Expression ◽

The Metabolic Syndrome ◽

Mammalian Cell Lines ◽

Phosphoinositide 3 Kinase

In the present study, we investigated the activity of the thiazide-sensitive NCC (Na+–Cl− co-transporter) in experimental metabolic syndrome and the role of insulin in NCC activation. Renal responses to the NCC inhibitor HCTZ (hydrochlorothiazide), as a measure of NCC activity in vivo, were studied in 12-week-old ZO (Zucker obese) rats, a model of the metabolic syndrome, and in ZL (Zucker lean) control animals, together with renal NCC expression and molecular markers of NCC activity, such as localization and phosphorylation. Effects of insulin were studied further in mammalian cell lines with inducible and endogenous expression of this molecule. ZO rats displayed marked hyperinsulinaemia, but no differences in plasma aldosterone, compared with ZL rats. In ZO rats, natriuretic and diuretic responses to NCC inhibition with HCTZ were enhanced compared with ZL rats, and were associated with a decrease in BP (blood pressure). ZO rats displayed enhanced Thr53 NCC phosphorylation and predominant membrane localization of both total and phosphorylated NCC, together with a different profile in expression of SPAK (Ste20-related proline/alanine-rich kinase) isoforms, and lower expression of WNK4. In vitro, insulin induced NCC phosphorylation, which was blocked by a PI3K (phosphoinositide 3-kinase) inhibitor. Insulin-induced reduction in WNK4 expression was also observed, but delayed compared with the time course of NCC phosphorylation. In summary, we report increased NCC activity in hyperinsulinaemic rodents in conjunction with the SPAK expression profile consistent with NCC activation and reduced WNK4, as well as an ability of insulin to induce NCC stimulatory phosphorylation in vitro. Together, these findings indicate that hyperinsulinaemia is an important driving force of NCC activity in the metabolic syndrome with possible consequences for BP regulation.

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Role of mechanical cues and hypoxia on the growth of tumor cells in strong and weak confinement: A dual in vitro–in silico approach

Science Advances ◽

10.1126/sciadv.aaz7130 ◽

2020 ◽

Vol 6 (13) ◽

pp. eaaz7130 ◽

Cited By ~ 1

Author(s):

V. Le Maout ◽

K. Alessandri ◽

B. Gurchenkov ◽

H. Bertin ◽

P. Nassoy ◽

...

Keyword(s):

In Silico ◽

Time Course ◽

Growth Dynamics ◽

Tumor Model ◽

Mechanistic Modeling ◽

Physical Factors ◽

Factors Affecting ◽

Numerical Studies

Characterization of tumor growth dynamics is of major importance for cancer understanding. By contrast with phenomenological approaches, mechanistic modeling can facilitate disclosing underlying tumor mechanisms and lead to identification of physical factors affecting proliferation and invasive behavior. Current mathematical models are often formulated at the tissue or organ scale with the scope of a direct clinical usefulness. Consequently, these approaches remain empirical and do not allow gaining insight into the tumor properties at the scale of small cell aggregates. Here, experimental and numerical studies of the dynamics of tumor aggregates are performed to propose a physics-based mathematical model as a general framework to investigate tumor microenvironment. The quantitative data extracted from the cellular capsule technology microfluidic experiments allow a thorough quantitative comparison with in silico experiments. This dual approach demonstrates the relative impact of oxygen and external mechanical forces during the time course of tumor model progression.

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The relationship between motor activity and transmural potential difference in the guinea pig intestine in vitro: is there a neural link?

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y86-169 ◽

1986 ◽

Vol 64 (7) ◽

pp. 993-998 ◽

Cited By ~ 8

Author(s):

Beverley Greenwood ◽

Stephanie Diamant ◽

J. S. Davison

Keyword(s):

Guinea Pig ◽

Motor Activity ◽

Colonic Motility ◽

Potential Difference ◽

Histological Data ◽

The Relationship ◽

Spontaneous Fluctuations ◽

Pig Jejunum

The aim of the experiments was to examine, in vitro, the role of the enteric nervous system in the relationship between motor activity and transmural potential difference (PD) in the guinea pig jejunum and colon using the nerve blocking agents tetrodotoxin (TTX) and aconitine. Histological data showed that perfusion of the intestinal segments with gassed Hepes solution was essential for the maintenance of transmural PD. Disruption of the mucosa was associated with a loss of spontaneous fluctuations in transmural PD without any loss of spontaneous motor activity. Under spontaneous conditions, a neural pathway exists linking jejunal and colonic motility with transmural PD. However, in some cases a mechanical link was also apparent, as an attenuated TTX and aconitine–resistant component.

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Binding of 63Ni(II) to Ultrafiltrable Constituents of Rabbit Serum In Vivo and In Vitro

Clinical Chemistry ◽

10.1093/clinchem/21.4.521 ◽

1975 ◽

Vol 21 (4) ◽

pp. 521-527 ◽

Cited By ~ 16

Author(s):

Noritake Asato ◽

Maria van Soestbergen ◽

F William Sunderman

Keyword(s):

Rabbit Serum ◽

Total Serum ◽

In Vivo Experiments ◽

The Mean ◽

Layer Chromatography ◽

In Vivo Administration ◽

Mean Concentration

Abstract Binding of 63Ni(Il) to ultrafiltrable constituents of rabbit serum was studied (a) after in vitro incubation (2 h, 37 °C) of rabbit serum with 63NiCl2 (10-100 µmol/liter), and (b) at intervals (0.25-2 h) after in vivo administration of 63NiCl2 (40-160 µmol/kg body wt, i.v.). Serum ultrafiltrates were fractionated by thin-layer chromatography, and the separated compounds made visible by autoradiography and by ninhydrin staining. Several (≃5) ultrafiltrable 63Ni-complexes were demonstrable as distinct radiodense 63Ni-bands with chromatographic mobilities corresponding to those of ninhydrin-positive bands. Unbound 63Ni(II) was not detected in serum ultrafiltrates in either the in vitro or in vivo experiments. In sera (n = 10) incubated in vitro with 63Ni(II) (10 µmol/ liter), the mean percentage of ultrafiltrable 63Ni was 36% (range = 33-38) of total serum 63Ni. In contrast, in sera (n = 10) obtained 2 h after i.v. injection of 63Ni(II) (40 µmol/kg), the mean concentration of total serum 63Ni was 10.8 µmol/liter (range = 6-14), and the mean percentage of ultrafiltrable 63Ni was 15% (range = 9-21) of total serum 63Ni. The disparity between the percentages of ultrafiltrable 63Ni obtained in vitro and in vivo was obviated when the in vivo experiments were performed in rabbits bilaterally nephrectomized, with ligated common bile ducts. This investigation confirms the existence of several nickel receptors in serum ultrafiltrates and substantiates the role of ultrafiltrable complexes in the excretion of nickel.

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Hyperaggregability Of Platelets In Cancer, Especially In Reference To Genesis Of DIC

10.1055/s-0038-1653313 ◽

1981 ◽

Author(s):

H Yamazaki ◽

Y Yahara ◽

T Motomiya ◽

K Tanoue ◽

I Isohisa ◽

...

Keyword(s):

Cancer Patients ◽

Time Course ◽

Mean Value ◽

Activated Partial Thromboplastin Time ◽

Healthy Controls ◽

Triggering Mechanism ◽

Coagulation Abnormalities ◽

Activated Platelets ◽

The Mean

To clarify the role of platelets in the genesis of DIC in cancer, platelets of cancer patients with and without DIC were examined. Patients studied were 29 cases with cancer in stomach, 17 in lung, 7 in pancreas, 6 in liver (hepatoma), 6 in throat, nose and jaw, 2 in the gall bladder and bilary duct, 2 in uterus and 1 each in the small bowel, rectum and prostate, and 1 each with osteosarcoma, mesothelioma and chorionepithelioma. All patients were in stage 3 or 4. 105 healthy controls were also studied. They were evaluated on a scale of coagulation abnormalities, one point was given for each of the following criteria full-filled, and the score (0 to 4) was used. 1. Platelet count<150xl03Anl. 2. Prothrombin time prolonged more than 1 sec over control and/or activated partial thromboplastin time prolonged more than 10 sec over control. 3. Fibrinogen<250 mg/dl (mean fibrinogen value of the cancer patients minus 1 SD). 4. FDP>20 µg/ml. The patients were distributed with 27 % for score 0, 38 % for 1, 20 % for 2, 7 % for 3 and 8 % for 4. Degrees of abnormality in groups with scores of 3 and 4 were significant when compared to scores 0 and 1, but score 2 was not clearly distinguishable. Platelet mode volume in score 4 was smaller than the other groups. Platelet aggregation by adrenaline and ADP decreased in score 3 and 4, while it increased significantly in score 0 and 1 respectively (P<0.01 -0.05). The mean value of plasma β-TG in the cancer patients as a whole (44±24 ng/ml) was significantly higher than that of control (22±13 ng/ml)(P<0.01). PF4 showed the same tendency. During the time course of the disease, hyperaggrega- bility of platelets associated with increases in β-TG and PF4 was observed before an appearance of DIC syndrome in several cases. The results suggest the existence of hyperfunction of platelets in cancer patients and the possibility of triggering mechanism of such activated platelets in the genesis of DIC in cancer.

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Two Quenchers Formed During Photodamage of Phostosystem II and The Role of One Quencher in Preemptive Photoprotection

Scientific Reports ◽

10.1038/s41598-019-53030-7 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 1

Author(s):

Alonso Zavafer ◽

Ievgeniia Iermak ◽

Mun Hon Cheah ◽

Wah Soon Chow

Keyword(s):

Chlorophyll Fluorescence ◽

Photosystem Ii ◽

Time Course ◽

Physiological Role ◽

Reaction Centre ◽

Time Resolved ◽

Fluorescence Quencher

AbstractThe quenching of chlorophyll fluorescence caused by photodamage of Photosystem II (qI) is a well recognized phenomenon, where the nature and physiological role of which are still debatable. Paradoxically, photodamage to the reaction centre of Photosystem II is supposed to be alleviated by excitation quenching mechanisms which manifest as fluorescence quenchers. Here we investigated the time course of PSII photodamage in vivo and in vitro and that of picosecond time-resolved chlorophyll fluorescence (quencher formation). Two long-lived fluorescence quenching processes during photodamage were observed and were formed at different speeds. The slow-developing quenching process exhibited a time course similar to that of the accumulation of photodamaged PSII, while the fast-developing process took place faster than the light-induced PSII damage. We attribute the slow process to the accumulation of photodamaged PSII and the fast process to an independent quenching mechanism that precedes PSII photodamage and that alleviates the inactivation of the PSII reaction centre.

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Overexpression of BRE in Pediatric MLL-Rearranged Acute Myeloid Leukemia Associated with t(9;11)(p22;q23).

Blood ◽

10.1182/blood.v114.22.3471.3471 ◽

2009 ◽

Vol 114 (22) ◽

pp. 3471-3471

Author(s):

Brian Balgobind ◽

C. Michel Zwaan ◽

Susan T.C.J.M. Arentsen-Peters ◽

Dirk Reinhardt ◽

Ursula Creutzig ◽

...

Keyword(s):

Gene Expression ◽

Myeloid Leukemia ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Apoptotic Effect ◽

The Mean ◽

Pediatric Aml ◽

Acute Myeloid

Abstract Abstract 3471 Poster Board III-359 One important cytogenetic subgroup of pediatric acute myeloid leukemia (AML) is characterized by translocations of chromosome 11q23, which accounts for 15 to 20% of all cases with an evaluable chromosome analysis. In most of these cases, the mixed lineage leukemia (MLL) gene is involved. More than 50 fusion translocation partners of the MLL gene have been identified and outcome differs by translocation partner, suggesting differences in the biological background. So far these biological differences have not been unravelled. Therefore, we investigated the gene expression profiles of MLL-rearranged subgroups in pediatric AML in order to discover and identify the role of differentially expressed genes. Affymetrix Human Genome U133 plus 2.0 microarrays were used to generate gene expression profiles of 257 pediatric AML cases, which included 21 pediatric AML cases with t(9;11)(p22;q23) and 33 with other MLL-rearrangements. With these profiles, we were able to identify a specific gene expression signature for t(9;11)(p22;q23) using an empirical Bayes linear regression model (Bioconductor package: Limma). This signature was mainly determined by overexpression of the BRE (brain and reproductive organ-expressed) gene. The mean average VSN normalized expression for BRE in the t(9;11)(p22;q23) subgroup was 3.7-fold higher compared with that in other MLL-rearranged cases (p<0.001). Validation by RQ-PCR confirmed this higher expression in t(9;11)(p22;q23) cases (p<0.001). In addition, we confirmed that overexpression of BRE was predominantly found in t(9;11)(p22;q23) in an independent gene expression profile cohort (Ross et al, Blood 2002). Remarkably, MLL-rearranged cases with a BRE expression higher than the mean expression showed a significant better 3 year disease free survival than MLL-rearranged cases with a lower expression (80±13% vs. 30±10%, p=0.02). Previously, overexpression of BRE has been described in hepatocellular carcinomas (HCC) (Chang et al., Oncogene 2008) and an anti-apoptotic effect was described. We transfected BRE in the monomac-1 cell line, which harbors a t(9;11)(p22;q23). We did not find a proliferative advantage for BRE overexpression using a BrDU-assay nor changes in drug sensitivity, indicating that the anti-apoptotic effect as described for HCC in vivo could not be confirmed in vitro in AML. In conclusion, overexpression of the BRE gene is predominantly involved in pediatric MLL-rearranged AML with t(9;11)(p22;q23). Moreover, high expression of BRE showed a favorable prognosis. We did not find any influence of BRE expression on cell proliferation or apoptosis in vitro. This indicates that further studies involving the role of the MLL-fusion protein on BRE transcription are necessary to unravel the leukemogenic role in pediatric AML. Disclosures No relevant conflicts of interest to declare.

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Dual Sensory-Motor Function for a Molluskan Statocyst Network

Journal of Neurophysiology ◽

10.1152/jn.00753.2003 ◽

2004 ◽

Vol 91 (1) ◽

pp. 336-345 ◽

Cited By ~ 36

Author(s):

R. Levi ◽

P. Varona ◽

Y. I. Arshavsky ◽

M. I. Rabinovich ◽

A. I. Selverston

Keyword(s):

Search Behavior ◽

Motor Program ◽

Hunting Behavior ◽

Marine Mollusk ◽

Receptor Cells ◽

Motor Nerves ◽

Clione Limacina ◽

Biologically Based Model

In mollusks, statocyst receptor cells (SRCs) interact with each other forming a neural network; their activity is determined by both the animal's orientation in the gravitational field and multimodal inputs. These two facts suggest that the function of the statocysts is not limited to sensing the animal's orientation. We studied the role of the statocysts in the organization of search motion during hunting behavior in the marine mollusk, Clione limacina. When hunting, Clione swims along a complex trajectory including numerous twists and turns confined within a definite space. Search-like behavior could be evoked pharmacologically by physostigmine; application of physostigmine to the isolated CNS produced “fictive search behavior” monitored by recordings from wing and tail nerves. Both in behavioral and in vitro experiments, we found that the statocysts are necessary for search behavior. The motor program typical of searching could not be produced after removing the statocysts. Simultaneous recordings from single SRCs and motor nerves showed that there was a correlation between the SRCs activity and search episodes. This correlation occurred even though the preparation was fixed and, therefore the sensory stimulus was constant. The excitation of individual SRCs could in some cases precede the beginning of search episodes. A biologically based model showed that, theoretically, the hunting search motor program could be generated by the statocyst receptor network due to its intrinsic dynamics. The results presented support for the idea that the statocysts are actively involved in the production of the motor program underlying search movements during hunting behavior.

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IL-17 affects progression, metastasis, and recurrence of laryngeal cancer via the inhibition of apoptosis through activation of the PI3K/AKT/FAS/FASL pathways

10.21203/rs.2.12638/v1 ◽

2019 ◽

Author(s):

Yang Song ◽

Ming Yang ◽

Jianhong Zhang ◽

Yan Sun ◽

Ye Tao ◽

...

Keyword(s):

Laryngeal Cancer ◽

Time Course ◽

Clinical Stage ◽

Immune Surveillance ◽

Disease Recurrence ◽

Tumor Promoter ◽

Interleukin 17 ◽

Normal Tissues

Abstract Background. Cytokines play important roles in development and prognosis of laryngeal cancer (LC). Interleukin-17 (IL-17) from a distinct subset of CD4 + T-cells may significantly induce cancer-elicited inflammation to prevent cancer cells from immune surveillance. Methods. The expression levels of IL-17 were examined among 60 patients with LC. Immunofluorescence co-localization experiments were performed to verify the localization of IL-17 and FAS/FASL in Hep-2 and Tu212 cells. IL-17 was silenced for expression in LC cell lines by siRNA techniques for determination of the role of IL-17 in LC. Results. In our LC patients, cytokines were dysregulated in LC tissues compared with normal tissues. We found that IL-17 was overexpressed in a cohort of 60 LC tumors paired with non-tumor tissues. Moreover, high IL-17 expression was significantly associated with advanced T category, late clinical stage, differentiation, lymph node metastasis, and disease recurrence. In addition, the time-course expression of FAS and FASL was observed after stimulation and treatment with IL-17 stimulator. Finally, in vitro experiments demonstrated that IL-17 functioned as an oncogene by inhibiting the apoptosis of LC cells via the PI3K/AKT/FAS/FASL pathways. Conclusions. Taken together, our findings for the first time demonstrate the role of IL-17 as a tumor promoter and a pro-metastatic factor in LC, indicating that IL-17 may have an oncogenic role and serve as a potential prognostic biomarker and therapeutic target in LC.

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Ovarian superstimulation with FSH in Wagyu breed bovine donors impacts folicular dynamics but does not improve the amount of embryos

Research Society and Development ◽

10.33448/rsd-v10i10.18811 ◽

2021 ◽

Vol 10 (10) ◽

pp. e165101018811

Author(s):

Fabio Marcelo de Queiróz ◽

Márcia Aparecida Andreazzi ◽

Fábio Luiz Bim Cavalieri ◽

Isabele Picada Emanuelli ◽

Marcelo Marcondes Seneda ◽

...

Keyword(s):

Animal Origin ◽

World Population ◽

Livestock Farming ◽

Oocyte Donor ◽

The Mean ◽

Group 2 ◽

Group 1 ◽

Donor Cows

The increase of the world population generates the need to raise the production of food of vegetal and animal origin. In Brazil, livestock farming has evolved, demonstrating the important role of the country in the production of food. In this way, researchers of this productive chain have been looking for technologies related to production and reproduction, above all, to the use of reproduction biotechnologies, seeking to increase the production of different bovine breeds. Thus, the objective of this research was to investigate the efficacy of ovarian FSH super stimulation in bovine Wagyu oocyte donor females on follicular dynamics and in vitro embryo production. Twelve Wagyu animals, aged 12 to 24 months, randomly distributed in a crossover design were used in two groups: Group 1= animals not stimulated with FSH and Group 2= animals stimulated with FSH. The follicular, oocyte and embryonic variables were evaluated. It was observed that ovarian overstimulation in Wagyu oocyte donor cows with FSH improved the mean and large follicles but reduced the rate of oocyte recovery and, despite the best percentage of viable oocytes, there was no improvement in the amount of embryos produced in vitro.

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